The overall objective of this project is to better understand novel cellular and molecular aspects of adaptive and innate immune responses in the channel catfish (Ictalurus puntatus), an immunologically well-characterized teleost model system of considerable scientific and economic importance. The first aim of the proposed studies deals with understanding the complex genetic organization of the teleost IgH locus, which encodes various IgD isotypes from different genes within the locus. The different IgD forms will be studied with respect to their structure, transcriptional regulation, and role in teleost adaptive immune responses. In addition, the mechanism by which thioredoxin activates teleost B cells will be investigated with regard to cellular expression of IgM and IgD isotypes. The second aim focuses on a diversified V region containing family of novel immune-type receptors (NITR) that exhibit structural diversity with respect to number of extracellular domains, and presence of cytoplasmic activating or inhibitory motifs. Studies are proposed to investigate whether or not teleost NITR molecules have functions analogous to the various receptor products encoded within the human leukocyte receptor complex. These studies include assessment of expression, target recognition, and regulation of innate immune responses. The proposed work is expected to yield novel information concerning the functional roles these potentially important, but poorly understood, molecules play in teleost immune responses. Furthermore, these molecules may prove important in understanding the more fundamental aspects of the evolutionary divergence of adaptive and innate immune functions.